The role of vitamin D3 in signaling pathways – potential anticancer properties of calcitriol and its analogues

Abstract

Vitamin D, for many years after the discovery, primarily was associated with bone metabolic processes. Currently, many studies indicate its beneficial effect in the prevention and treatment of many diseases, including cancer. However, deficiency of vitamin D is associated with greater tendency to get sick and worse prognosis in treatment, especially cancer. Calcitriol, an active form of vitamin D (1.25(OH)2D3) and its analogues have a pleiotropic activity, including anti-cancer properties. Many studies indicate, that the active forms of vitamin D3 may show anti-proliferative effects in cancer cells by inhibiting the cell cycle, inducing differentiation or leading to apoptosis and enhancing autophagy. Also, extremely important are the possibilities of reducing the invasiveness of tumours through the influence on angiogenesis or adhesion and others. Especially, the anti-cancer role of vitamin D3 is suggested in the case of tumors whose cells express VDR receptors. Interestingly, many cancer cells not only express the VDR receptors, but also due to the expression of CYP27B1 and CYP24A hydroxylases, they can regulate metabolism of calcitriol. Many of the studies using vitamin D3 show that calcitriol and its analogues, due to the influence on cancer cells, can play promising roles in anticancer therapies. Consider the broad pleiotropism of the action of active metabolites of vitamin D3 and the development of research in this field, the current work presents the effect of active forms of vitamin D on some signalling pathways and the regulation of selected proteins in various cancers.